The bright prospects of increasing life expectancy in many populations around the world are tempered by an alarming increase in amyloid peptide-related neurodegenerative disorders. Alzheimer's disease, the most frequent among these conditions, causes an inexorable loss of memory and other cognitive functions. Although the etiology of most AD cases remains elusive, several key features of this disease can be simulated in transgenic mice, making them amenable to experimental analysis and manipulation. Indeed, hAPP mice are used increasingly to assess novel AD treatments. Amyloid plaques have remained the primary pathological outcome measure in these studies, although their contribution to AD-related cognitive deficits is controversial. In fact, it remains to be determined which of the many pathological and biochemical alterations identified in AD and related transgenic models contribute most critically to the decline in neuronal functions.
Currently, mouse models of amyloid peptide-related neurological disorders such as Alzheimer's Disease are used for identifying agents that are useful for treating such disorders. The efficacy of a given test agent is typically determined by assessing and scoring behavioral traits such as learning and memory. An example of such a test is the water maze test. Such tests are time-consuming, may be somewhat subjective, and are subject to a high degree of variability and imprecision.
There is a need in the art for improved methods of detecting neurological disorders associated with neurotoxic levels of amyloid peptide. The present invention addresses this need, and provides an alternative read-out for efficacy of a test agent on treating cognitive impairment.
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